JPH08112333A - Method for packing freeze drying agent of prefilled syringe of type to dissolve when needed - Google Patents

Abstract

PURPOSE: To make it possible to freeze dry a medicinal liquid for production of a powdered medicine in a half plugged state after charging this medicinal liquid into an injection barrel. CONSTITUTION: The injection barrel 1 has a bypass part 2 and a needle mounting part 14 is hermetically sealed by a packing, lure chip 15, cap, etc. The needle mounting part 14 of the injection barrel 1 is inserted into a jig and is held upright. After the medicinal liquid 16 for production of the powdered medicine is charged therein, an intermediate gasket 4 by which the interior of the injection needle communicates with the outdoor air in a half- plugging state and which is capable of hermetically sealing the interior thereof in a hermetically plugged state is mounted at the top end of the injection barrel 1 in the half-plugging state and the injection barrel is charged into a freeze drying machine, by which the medicinal liquid is freeze dried and the powdered medicine 17 is prepd. The intermediate gasket 4 is thereafter pushed by plugging equipment down into the part just before the bypass part 2 of the injection barrel 1 to hermetically seal the barrel. The injection barrel is taken out of the freeze drying machine and a dissolving liquid 18 is packed into a dissolving liquid housing section 5. The other of this dissolving liquid housing section 5 is hermetically sealed by a gasket 13. As a result, the need for manual labor to put the temporary plugging after the freeze drying into the half plugging state is eliminated and the productivity is improved.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for filling a lyophilized preparation of a pre-filled syringe which is a dissolution type before use, which is one of medical kit products for injection, which is a combination of a medicine and an administration system.

[0002]

2. Description of the Related Art In a non-kit administration system such as an ampoule and a vial formulation, the content drug solution varies in the amount sucked into a syringe, and it is difficult to accurately collect the indicated amount with a viscous drug solution. , Foreign matter such as glass fragments when cutting ampoules or coring when threading a rubber stopper.
On the other hand, injectable medical kit products that combine a drug and an administration system can reduce the risk of microbial contamination, prevent errors during drug administration, and provide quick response during an emergency compared to non-kit administration systems. It has medical advantages such as improvement of quality, waste of chemicals, reduction of property cost by simplifying inventory management, convenience and safety, and reduction of workload.

For this reason, many medical kit products have been recently developed and sold. Among pre-filled disposable syringes (pre)
filled disposable syring
e, hereinafter referred to as a prefilled syringe) is a system that provides a drug solution in a form that is pre-filled in a syringe, and has excellent responsiveness in an emergency. In recent years, a solid-state drug and an attached solution are provided in a single syringe. A pre-filled syringe that can be dissolved before use has been developed and is widely sold. As a ready-to-use prefilled syringe that is used to mix a solid-state drug with an attached solution or two types of drug solutions at the time of use, a needle mounting part of a syringe barrel having a bypass part is wound with aluminum luer tip through packing. After that, charge the freeze-dried preparation into the syringe barrel with the needle mounting part facing down, press the intermediate gasket to just before the bypass part of the syringe barrel to seal the plug, then inject the solution, and re-insert the pusher mounting screw hole. Dissolving type prefilled syringes for use by pushing in the gaskets and sealing them are sold.

When using the dissolution type prefilled syringe at this time, the pusher is screwed into the pusher mounting screw hole of the gasket of the injection cylinder, and when the pusher is pushed in as it is, the intermediate gasket moves to the bypass part and the bypass part. The lysate flows into the freeze-dried preparation encapsulation part via the. When the pusher is further pushed in, the gasket comes into contact with the intermediate gasket, and all of the dissolution liquid flows into the freeze-dried preparation encapsulation portion to dissolve the freeze-dried preparation. After that, a double-point injection needle is passed through the packing and inserted into the aluminum luer tip to complete the preparation for administration. The in-use dissolution-type prefilled syringe charges the freeze-dried preparation into the syringe barrel, so the work of charging the freeze-dried preparation is mechanically complicated as compared with the case of charging the drug solution, and it takes a lot of time and productivity. Has the drawback of being low.

As a method of solving the above-mentioned drawbacks, an injection cylinder whose tip needle mounting portion is sealed with packing, luer tip, cap or the like is inserted into a jig and stood up, and a medicinal solution for producing a powdered drug is charged, followed by injection. After temporarily freeze the intermediate gasket on the upper end of the cylinder and freeze-dry it, push the intermediate gasket to the front of the bypass part of the injection cylinder to seal it tightly, fill the dissolving liquid storage part with the dissolving liquid and close the other side of the dissolving liquid storage part. A method has been proposed in which a gasket is pushed in and tightly plugged.

[0006]

An injection cylinder in which the tip needle mounting portion is sealed with packing, a luer tip, a cap, etc. is inserted into a jig to stand up, and a drug solution for producing a powdered drug is charged. The method of freeze-drying by temporarily plugging the intermediate gasket is to push the intermediate gasket mechanically just before the bypass section of the injection cylinder after the freeze-drying is completed. Impossible,
There is a drawback that manpower is required to make the intermediate gasket of the temporary stopper half-capped and the productivity is low. For this reason, the development of a freeze-dried preparation filling method for a pre-filled syringe ready for use that can be freeze-dried in a half stoppered state after charging a liquid medicine for powder drug preparation into an injection cylinder is strongly desired.

An object of the present invention is to solve the above-mentioned drawbacks of the prior art, and to freeze-dry a ready-to-use dissolution type prefilled syringe which can be freeze-dried in a half stoppered state after charging a syringe with a drug solution for producing a powder drug. It is to provide a method for filling a formulation.

[0008]

[Means for Solving the Problems] The inventors of the present invention have made extensive studies to achieve the above object. As a result, after inserting the injection cylinder with the tip needle mounting part sealed with packing, lure tip, cap, etc. into the jig and charging it with the drug solution for powdered drug manufacturing, the injection cylinder at the top end of the injection cylinder is in the half stoppered state. The inside and outside air communicate with each other, and an intermediate gasket that can be tightly closed by pushing it to the front of the bypass part is attached in a half-stopped state and vacuum freeze-dried, or it has intermittent recesses in the circumferential direction and is inserted into the upper end of the syringe barrel. A member that can be connected to the inside of the syringe and the outside air communicates with the member when the stopper is half closed, and is attached with an intermediate gasket that can be sealed in a tightly closed state and vacuum freeze-dried. Therefore, it was found that the other side of the dissolution liquid storage section can be sealed by filling the dissolution liquid storage section with the dissolution liquid and pressing the gasket for sealing the other side of the dissolution solution storage section.

That is, according to the present invention, in a method for filling a freeze-dried preparation into a syringe having a bypass portion and having a needle mounting portion sealed with packing, luer tip, cap, etc., the needle mounting portion of the syringe barrel is inserted into a jig. Upright, and after charging the drug solution for powdered drug manufacturing, the inside of the injection cylinder communicates with the outside air when the stopper is half closed, and an intermediate gasket that can be sealed in a closed stopper is attached to the stopper and frozen. After being placed in a dryer and freeze-dried to give a powdered drug, the intermediate gasket is pushed up to the front of the bypass section of the injection cylinder with a stoppering device to seal and then taken out from the freeze-dryer and the solution storage section is filled with the solution. Then, the other side of the solution storage section is tightly closed with a gasket, which is a method for filling a freeze-dried preparation for a pre-filled syringe for dissolution before use.

Further, in a method for filling a freeze-dried preparation into an injection cylinder having a bypass part and having a needle mounting part sealed with packing, luer tip, cap, etc., the needle mounting part of the injection cylinder is inserted into a jig to stand upright. After charging the liquid medicine for powder drug production, insert a member having intermittent recesses in the circumferential direction at the upper end of the injection cylinder, and in the half-stopped state, the inside of the injection cylinder communicates with the outside air, and the plugged state After mounting the intermediate gasket that can be sealed with a semi-stoppered state, insert it into the freeze dryer and vacuum freeze-dry it into a powdered drug, then push the intermediate gasket up to the front of the bypass section of the syringe barrel with the stoppering device and seal it tightly. A method for filling a lyophilized preparation for a pre-dissolved pre-filled syringe for use, wherein the solution is taken out from the freeze-dryer, the solution storage section is filled with the solution and the other side of the solution storage section is sealed with a gasket.

[0011]

According to the present invention, the needle mounting portion of the injection cylinder is inserted into the jig to stand upright, and the drug solution for powder drug production is charged, and then the inside of the injection cylinder and the outside air communicate with each other when the upper end of the injection cylinder is half plugged. Then, attach an intermediate gasket that can be sealed in a tightly closed state to a half stoppered state, insert it into a freeze dryer and freeze-dry it to make a powdered drug, then push the intermediate gasket up to the front of the bypass section of the syringe barrel with a stoppering facility. The intermediate gasket can be freeze-dried in a half-stopped state by filling the dissolution liquid storage unit with the dissolution liquid and sealing the other side of the dissolution liquid storage unit with a gasket. The intermediate gasket can be automatically pushed by the stoppering device from the half-capped state to the front of the bypass part, and the manpower required to put the temporary stopper into the half-capped state after freeze-drying is not required, thus improving productivity. Can be planned .

Further, according to the present invention, after the needle mounting portion of the injection cylinder is inserted into the jig to stand upright and the drug solution for powder drug production is charged therein, the injection cylinder has a circumferentially intermittent recess at the upper end thereof. Insert the member, and in the half stoppered state, the inside of the syringe communicates with the outside air in the half stoppered state, attach an intermediate gasket that can be sealed in the closed stopper state to the half stoppered state, insert it into the freeze dryer and freeze dry. After making the powdered medicine, push the intermediate gasket to the front of the bypass part of the injection cylinder with a stoppering device to seal it tightly, take it out from the freeze dryer, fill the dissolution liquid storage part with the dissolution liquid, and gasket the other side of the dissolution liquid storage part. The intermediate gasket can be freeze-dried to the member in a half stoppered state by tightly plugging with the member, and the intermediate gasket can be automatically pushed to the front side of the bypass section by the stoppering device through the member in the freeze dryer. freeze drying Provisionally stoppered becomes unnecessary manpower for the semi-stoppered state, we are possible to improve the productivity.

In the semi-stoppered state according to the present invention, the inside of the injection cylinder communicates with the outside air, and the intermediate gasket which can be sealed in the closed state is a convex portion between a plurality of concave grooves of a gasket having a plurality of concave grooves on the periphery and The bottom convex part is partially cut out, and in the half stoppered state, the convex part between the plurality of concave grooves of the intermediate gasket and the bottom convex part are partially cut out, so that the convex part between the plurality of concave grooves is partially cut out. The inside of the syringe and the outside air communicate with each other by the notches and the plurality of recessed grooves of the lower portion and the lowermost convex portion, and when the intermediate gasket is pushed in front of the bypass portion of the syringe barrel, the uppermost convex portion tightly plugs. For this reason, it is preferable that the uppermost protrusion has a thickness that is at least twice the thickness of the protrusion between the other plurality of concave grooves and the lowermost protrusion. Examples of the material for the intermediate gasket include butyl rubber, epichlorohydrin rubber, isoprene, butadiene rubber, and styrene-butadiene rubber.

Further, the member having intermittent recesses in the circumferential direction, which is inserted into the upper end of the syringe barrel in the present invention, has intermittent recesses in the circumferential direction of the upper end, and has the same inner diameter as the inner diameter of the syringe barrel and a lower portion. Most of the gripping the upper end of the syringe with the same inner diameter as the outer diameter of the barrel consists of a plurality of divided legs, and in the half stoppered state, the convex part between the concave grooves of the intermediate gasket and the convex part at the bottom are Due to the partial cutout, the intermittent recesses in the circumferential direction of the upper member, and the notches and the plurality of recessed grooves of the protrusions between the recessed grooves of the intermediate gasket and the bottommost protrusion,
When the inside of the syringe communicates with the outside air and the intermediate gasket is pushed in front of the bypass portion of the syringe, it is tightly plugged by the uppermost convex portion. Therefore, the half-capped state by the member and the intermediate gasket can be applied to an injection cylinder in which it is difficult to provide a recessed portion in the circumferential direction of the upper end of the injection cylinder or a collar-shaped grip like a glass injection cylinder. it can.

[0015]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The details of the present invention will be described below with reference to FIGS. 1 is an overall view of a syringe barrel of a pre-filled syringe of the present invention,
In the half stoppered state of the present invention, the inside of the syringe communicates with the outside air,
FIG. 3 is a side view of an intermediate gasket which can be sealed in a sealed state, FIG. 3 is an explanatory view of a method for filling a freeze-dried preparation of the present invention, and FIG. 4 shows a member having intermittent recesses in the circumferential direction which is inserted into the upper end of a syringe. FIG. 5A is a side sectional view, FIG. 5B is a plan view, FIG. 5C is a bottom view, and FIG. 5 is an explanatory view in the case where the member of FIG. 4 and an intermediate gasket are combined. In FIGS. 1 to 3, 1 is an injection cylinder for containing a powdered drug and a solution, 2 is a convex bypass provided in a powdered drug encapsulation portion 3 of the injection cylinder 1, 4
Is an intermediate gasket that tightly plugs between the powder drug enclosing portion 3 and the dissolved liquid enclosing portion 5, and has two recessed grooves 7 and 8 having a communicating portion 6.
And the notch 10 in the lowermost convex portion 9 and the intermediate convex portion 1
In the state of half-capped insertion into the syringe barrel 1 up to 1, the inside of the syringe barrel 1 communicates with the outside air by the recessed groove 7, the communicating portion 6, the recessed groove 8 and the notch 10 of the intermediate gasket 4, so that When the injection tube 1 is pushed up to the upper convex portion 12, the uppermost convex portion 12
It is configured to be plugged by. Reference numeral 13 is a gasket that tightly plugs the solution filling portion 5 of the injection cylinder 1, and is provided with a screw hole (not shown) for connecting a pusher. 14
Is a needle mounting portion of the injection cylinder 1 and is tightly wound by an aluminum luer tip 15 via a packing.

When the drug is filled in the injection barrel 1 of the above-mentioned pre-dissolved prefilled syringe, as shown in FIG. 3, the needle mounting portion 14 of the injection barrel 1 is wrapped and sealed with an aluminum luer tip 15 through a packing so as to be sealed. After that, the needle mounting portion 14 of the syringe barrel 1 is inserted into a jig (not shown) with the needle mounting portion 14 downward, and the jig is set upright.
The drug solution 16 for powder drug production is filled with the powder drug encapsulation portion 3 of the syringe barrel 1.
After that, the intermediate gasket 4 is inserted into the upper end of the injection cylinder 1 up to the intermediate convex portion 11 and mounted in a half stoppered state. In the half-plugged state in which the intermediate gasket 4 is inserted into the intermediate convex portion 11, the concave groove 7, the communicating portion 6, the concave groove 8,
Since the inside of the syringe 1 is communicated with the outside air through the notch 10, the water evaporated from the drug solution 16 for powder drug preparation is charged into a lyophilizer (not shown) and vacuum freeze-dried so that the water content evaporated from the concave portion of the intermediate gasket 4 will be reduced. Groove 7, communication part 6, concave groove 8, notch 10
It evaporates through and becomes the powdered medicine 17. When the freeze-drying of the drug solution for powder drug production 16 is completed, the intermediate gasket 4 is in a half stoppered state. Therefore, by automatically pressing the intermediate bypass 4 before the convex bypass 2 of the injection barrel 1 by a stoppering device (not shown), the stopper is sealed. You can After that, the injection cylinder 1 is taken out from the freeze-dryer (not shown), the dissolution liquid storage part 5 is filled with the dissolution liquid 18, and the other side of the dissolution liquid storage part 5 is tightly sealed with a gasket 13.
Complete drug loading.

4 to 5, reference numeral 41 designates a member having the same inner diameter as the syringe barrel, which has a circumferentially intermittent recessed portion 42 which is inserted into the upper end of the syringe barrel having no collar-shaped grip on the upper end.
43 is a leg part that grips the upper end of the syringe barrel having the same inner diameter as the syringe barrel outer diameter in the lower part of the member 41, and most of the vertical direction is divided into a plurality of legs, and 44 is a protrusion provided at the center of the lower part of each leg part 43,
Grip the outer surface of the syringe barrel. Reference numeral 45 denotes an intermediate gasket that allows the inside of the injection cylinder to communicate with the outside air through the recess 42 of the member 41 in the half stoppered state, and can be sealed by inserting into the injection cylinder, and is provided with a plurality of recessed grooves 46 and 47 in the periphery. When the notch 49 is provided in the lowermost convex portion 48 and the member 41 is in the half stoppered state, the concave portion 42 which is intermittent in the circumferential direction of the member 41, the concave groove 47 of the intermediate gasket 45, and the lowermost convex portion 48. The inside of the syringe is communicated with the outside air by the notch 49 of FIG.
It is configured to be tightly plugged with 0, 51.

In the case of filling a drug into an injection cylinder having no flange-shaped grip on the upper end of the above-mentioned dissolution type prefilled syringe, the needle mounting part of the injection cylinder is wrapped and sealed with an aluminum luer tip through a packing to seal it. After that, the needle mounting portion of the injection cylinder is inserted into a jig (not shown) to stand up, the drug solution for powder drug production is charged into the powder drug encapsulation portion of the injection cylinder, and then each leg portion 43 of the member 41 is attached to the upper end of the injection cylinder. After fitting the
Then, the intermediate gasket 45 is inserted in a half-plugged state. When the intermediate gasket 45 is in the half stoppered state, it is inserted through the intermittent concave portions 42 provided in the circumferential direction of the member 41, the concave groove 47 of the intermediate gasket 45 and the partial cutout 49 of the lowermost convex portion 48. Since the inside of the syringe communicates with the outside air, the drug solution for producing a powdered drug can be made into a powdered drug by charging it into a freeze dryer (not shown) and vacuum freeze drying. Intermediate gasket 45
Since it is in a half stoppered state, it can be automatically pushed by the stoppering device (not shown) up to the front of the convex bypass of the syringe barrel for a tight stopper. After that, the syringe is taken out from the freeze-dryer (not shown), the solution storage part is filled with the solution, and the other part of the solution storage part is sealed with a gasket to complete the drug filling. Therefore, it is possible to improve the productivity because it is not necessary to manually change the intermediate gasket from the temporary stopper to the half-capped state after freeze-drying the intermediate gasket with the temporary stopper as in the conventional case.

[0019]

As described above, according to the method of the present invention, since the drug solution for producing a powdered drug can be injected into the syringe barrel and the intermediate gasket can be freeze-dried in the half-stopped state, it is possible to use the stoppering device after freeze-drying to perform the intermediate treatment. The gasket can be pushed to the front side of the bypass portion of the injection cylinder to be tightly closed, so that it is not necessary to manually turn the temporary stopper into a half-stopped state after freeze-drying as in the conventional case, and productivity can be improved.

[Brief description of drawings]

FIG. 1 is an overall view of a syringe barrel of a pre-filled syringe which is a dissolution type before use of the present invention.

FIG. 2 is a side view of an intermediate gasket according to the present invention in which the inside of the injection cylinder is in communication with the outside air in the half stoppered state and can be sealed in a tightly stoppered state.

FIG. 3 is an explanatory diagram of a freeze-dried preparation filling method of the present invention.

FIG. 4 is a view showing a member having intermittent recesses in the circumferential direction, which is inserted into the upper end of the syringe barrel, and FIG.
The figure (b) is a plan view and the figure (c) is a bottom view.

5 is an explanatory view of a case where the member of FIG. 4 and an intermediate gasket are combined.

[Explanation of symbols]

 1 Injection Cylinder 2 Convex Bypass 3 Powdered Drug Encapsulation Part 4, 45 Intermediate Gasket 5 Dissolved Solution Encapsulation Part 6 Communication Part 7, 8, 46, 47 Recessed Groove 9, 48 Lowermost Convex Part 10, 49 Notch 11 Intermediate Convex Part 12 Uppermost convex portion 13 Gasket 14 Needle mounting portion 15 Almyr tip 16 Chemical liquid for powder drug production 17 Powdered drug 18 Dissolution liquid 41 Member 42 Recess 43 Leg 44 Protrusion 50, 51 Convex part

Claims (2)

[Claims] 1. A needle mounting part having a bypass part and packing,
In the method of filling a freeze-dried preparation into a syringe sealed with a lure tip, a cap, etc., insert the needle mounting part of the syringe into the jig and stand it up. In the stoppered state, the inside of the syringe communicates with the outside air, and an intermediate gasket that can be sealed in a tightly closed state is attached in a half-stoppered state, put in a freeze dryer and freeze-dried to make a powdered drug, then the intermediate gasket is injected. Push it to the front of the bypass part of the cylinder with a stoppering device to seal it tightly, and remove it from the freeze dryer.
A method for filling a freeze-dried preparation for a pre-filled syringe for dissolution, when the solution is stored in a solution storage part and the other part of the solution storage part is sealed with a gasket. 2. A needle mounting part having a bypass part and packing,
In the method of filling a freeze-dried preparation into a syringe sealed with a luer tip, a cap, etc., insert the needle mounting part of the syringe into a jig and stand it up, and after charging the drug solution for powdered drug production, make a circle around the top of the syringe. A member having intermittent recesses in the direction is inserted, and in the semi-stoppered state, the inside of the injection cylinder communicates with the outside air in the semi-stoppered state, and an intermediate gasket that can be sealed in a tightly closed state is attached to the half-stoppered state, and the freeze dryer is attached. Then, after freeze-drying it into a powdered drug, press the intermediate gasket to the front of the bypass section of the injection cylinder with the stoppering device to seal it tightly, remove it from the freeze dryer, and fill the solution storage section with the solution. A method for filling a freeze-dried preparation for a pre-filled syringe, which is a dissolution-type before use, characterized in that the other side of the solution storage section is sealed with a gasket.